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Post-Doc Wins Prestigious Cancer Research Award

When Wei Zhang was a graduate student in a research hospital lab, he’d encounter cancer patients going through therapy, knowing all too well the damage the treatment was causing to their bodies. “The patient’s body is crushed by the drugs, which work by mutating the DNA causing the cancerous cells to die, but normal cells also suffer,” says Zhang. Ten years on, Zhang is in a position where he can help develop therapies that target cancer more precisely and are kinder on the patient.

And an award from the Cancer Research Society will help him reach this goal.

Zhang, a senior post-doctoral fellow in the labs of Professors Sachdev Sidhu and Jason Moffat, of the University of Toronto’s Donnelly Centre and Department of Molecular Genetics, ranked first among 18 candidates to win this year’s Cancer Research Society/BMO Bank of Montreal Scholarship for the Next Generation of Scientists, it was announced earlier this month. The award supports early young investigators by providing $120,000 (CAD) in research funding, once they have obtained a faculty position at a Canadian research institution.

“Wei Zhang has all the attributes of a great scientist and mentor: creativity, perseverance, collegiality and the patience to deal with both peers and trainees,” says Sidhu, who is also Director of the Centre for Commercialization of Antibodies and Biologics and Senior Investigator at the Ontario Institute for Cancer Research. “I am confident he will make a great principal investigator and Canada will be fortunate to retain him in our midst.”

The award is expected to help Zhang’s application for a faculty position stand out in a fiercely competitive job market and secure research funds in the future.

“The award means that I proved to the selection committee of a university that I can attract competitive funding as a principal investigator,” says Zhang, who last year won the Mitacs award for Outstanding Innovation for creating proteins capable of destroying the deadly viruses behind the Middle East Respiratory Syndrome (MERS) and Congo-Crimean fever.

Zhang grew up in China and obtained a bachelor’s degree in Beijing. He then moved to Canada and received a master’s degree from Toronto’s York University and a PhD from U of T where he studied DNA damage and repair in the lab of molecular genetics professor, Dr. Daniel Durocher, at the Sinai Health System’s Lunenfeld-Tanenbaum Research Institute. It was during his PhD that Zhang realized that DNA damage could be a way in to target cancer cells more precisely without harming healthy tissue.

Healthy cells have two main systems in place to fix breaks in the DNA that can be caused by radiation or chemicals, for example. In cancer cells, however, one of these repair machineries is often disabled by mutations, leaving them uniquely vulnerable to drugs that block the remaining repair system.

That the approach works was shown by PARP inhibitors, new drugs that selectively block one DNA repair machinery to only kill the cancer cells without causing widespread side-effects.

With hundreds of proteins involved in DNA repair, any one of them is a potential drug target.

Zhang’s plan is to use protein engineering skills that he obtained in the Sidhu and Moffat labs to create new tools which will allow him to selectively target different parts of the DNA repair machinery.

Protein are complex molecules composed of different parts that do different things in the cell. Most research tools work like a power cut, where they block an entire protein instead of switching off just one light. This all-or-nothing type of intervention can cause side-effects that precise therapies could avoid.

“There is an urgent need for tool molecules, which can be generated using protein engineering, to probe the molecular processes driving DNA repair with unprecedented precision,” says Zhang.

Zhang’s initial focus will be on the so-called UBZ4 domain proteins, named after the part of the molecule with which they contact other proteins, and which are often mutated in people with Fanconi anemia, a rare inherited disease.

Calm and self-effacing, Zhang also harbors an unmistakable resolve to advance cancer research and to ultimately help patients.

“With protein engineering, we can create a new molecule that can do what we want it to do—for example to bind its partner much more strongly than the natural protein,” says Zhang. “And I want to use these proteins as tools to generate molecules that have the potential for cancer therapy.”